In a Different Key

by John Donvan

  In 1995, Portia set out on a recruitment tour, traveling to cities all over the United States to make in-person appeals, mostly to younger scientists, not only to persuade them to see that autism was a fascinating and promising window into their specialties—whether it be genetics, molecular biology, neuroscience, or something else—but also to see whether they would be willing to play by CAN’s rules.

  Around this time, Portia was introduced to an assistant professor of neurology at UCLA named Daniel Geschwind. As a courtesy to a fellow faculty member who was raising two autistic children, Geschwind agreed to a half-hour chat in his lab’s conference room. Three and a half hours later, the conversation was still going, and Geschwind was about to make the most momentous decision of his career. As he listened to Portia—this Hollywood art director who had somehow learned to talk the research “talk”—Geschwind felt himself getting pulled along. Portia was offering him a once-in-a-lifetime opportunity—even if it was a gamble—to be an early participant in a new and broad scientific endeavor. By the time they parted that day, Cure Autism Now had acquired a chairman for its scientific advisory board.

  It was a turning point for Cure Autism Now. Geschwind was the perfect leader for an organization that hoped to leave behind its own adolescence. While he accepted CAN’s rules about parental influence on funding, he believed that CAN needed to distance itself from the alternative-therapies crowd. Over the course of several months, the composition of its scientific advisory board underwent a transformation, losing several members whose viewpoints were less orthodox, while taking on scientists whose pedigrees came closer to those of the group that NAAR had put together, many of whom were still junior enough to take the same gamble Geschwind had.

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  BACK EAST, MEANWHILE, the Londons’ New Jersey living room began to fill with boxes during the week before the October 15 deadline. Scientists from across the country were sending in proposals in response to NAAR’s RFP letters. Each box represented one proposal, duplicated twenty times to be distributed among the members of NAAR’s scientific advisory board.

  When October 15 finally arrived, there was a total of twenty-seven boxes stacked up, waiting to be opened. Karen, who was Jewish, woke up finally understanding what a kid might feel like on Christmas morning. She and Eric sat on the living room floor, tore open the boxes, and dove into their contents. They were delighted to see that the proposals they were poring over were as solid as the places they came from were reputable. They heard from researchers at Duke University, Johns Hopkins University School of Medicine, the Kennedy-Krieger Institute, the University of California at Irvine, and fifteen other leading universities. This was no longer a pipe dream. Every proposal validated the case they had been making for two years—that a parent-run organization could shape and drive serious scientific inquiry into autism. A few weeks later, the scientific advisory board the Londons had created met at a hotel near Harvard to pick the proposals to fund from among the twenty-seven applicants.

  By that point, NAAR had raised nearly $850,000, and the goal was to disburse $150,000 in this first round of funding. The board divided it equally among five winners. Their studies ranged from using neuroimaging of the brain to explore the impact of high amounts of white brain matter seen in children with autism, to measuring the brain waves of kids with autism as they tried to speak, to the use of some new molecular detection methods to explore the possible role of a particular virus in provoking autistic behaviors.

  All the work produced out of this first round of funding added substantively to the scientific understanding of autism and produced publishable findings. Within a year, two of NAAR’s first grant recipients came to the attention of federal funders, who awarded them a combined $3.6 million to continue the investigations that NAAR’s money had launched. This was the Londons’ ideal scenario coming true. The “seed money” that had spread around to make autism appealing to researchers was catching the eye of other funders, who were also stepping up. It looked like the start of a virtuous cycle.

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  IN THE LATE spring of 1996, Jon Shestack had flown east to Washington to start lobbying Capitol Hill for increased spending on biomedical research. He was also headed for the National Institutes of Health, to share with scientists one of CAN’s biggest ideas for “hurrying up the science.” The particulars of the concept were so bold and radical that he had expected some excitement from the roomful of geneticists he was addressing. But as Shestack finished speaking that day, the chilly silence in the room told him otherwise. As the Hollywood autism dad looked around at the scientists’ faces, he reached for his wallet. It was time, again, to get out the picture of Dov.

  Cure Autism Now was ready to start spending money, and genetic research had moved into top place on its list of priorities. Once again, Dan Geschwind was making his influence felt. For months, he had been educating CAN’s founders on both the promise and the challenges of investigating autism’s genetic underpinnings. He told them that autism’s complexity pointed to quite a large number of genes being involved, and an even greater number of combinations of genes. Each of these combinations, interacting with some yet-to-be determined environmental factors, might represent a distinct pathway to having the condition. In other words, there might be many kinds of autism with a wide range of causes. Diving into each pathway by following genetic footprints would be vital to sorting out these complexities and designing interventions.

  Geschwind told CAN’s founders that when they started spending money on research, gene research should be a primary target, but he also explained that the answers would not come by studying the DNA of one or two individuals with the condition. The subtle and multifarious differences among people with autism demanded that researchers have access to the DNA of, at a minimum, hundreds of individuals. Moreover, in order to derive the most meaningful genetic information, the DNA of siblings offered the best opportunity for discovery.

  But there was one major obstacle: there was not a lab anywhere with that amount of genetic material from autistic siblings in its storage coolers. Because of the time and money it cost to find and analyze the DNA of just one set of donor siblings, most researchers had only a handful of specimens. Moreover, they all jealously guarded what little they had. Science was, after all, competitive. Glory and the ensuing financial reward came from being the “first and only” in making important discoveries. As a result, genetic researchers were loath to share their DNA specimens with one another, even though pooling their resources might lead to more meaningful discoveries faster.

  Then Portia came up with a bold idea: CAN would create its own collection of DNA. It would make it big, and it would make it available to the scientific community at large. CAN would do this by leveraging one of its unique strengths as an organization: its intimate connection to families. In short, Portia wanted to call on CAN’s network of parents to step up and volunteer their children as donors. CAN would do the recruiting, collect and store the DNA, and then make it available to any scientists who were committed to doing research on autism. It would be a massive “freebie” to the genetic labs of the world, because Cure Autism Now would be paying for everything.

  As Shestack always told the story afterward, the NIH geneticists were cold to the idea when he first presented it. Perhaps they felt it would be too disruptive to the status quo and that it went against the prevailing ethos of competition among scientists. That may well have been true, but there were also sound scientific reasons for thinking that a parent-run DNA-collection program would be a disaster. Collecting genetic material was not for amateurs, but CAN’s plan called for families to take their kids to a local doctor or clinic to draw blood, stick the sample in a mailer, and send it to CAN, who would then find a way to store it. Moreover, CAN had no reliable way to determine whether these kids actually merited a diagnosis of autism in the first place, nor would they know what specific combinations of autistic traits each child manifested. If it was to be presumed that different genetic pat
terns led to different “autisms,” then this sort of information was crucial. All in all, the CAN plan was likely to produce scientific garbage.

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  AND SO, CAN adjusted its plan; Jon and Portia went out and hired “magic man” Ed Berry. CAN would now be sending out an expert to get blood drawn the right way: safely, consistently, professionally. They had met Berry when, in their long round of efforts to get Dov’s medical treatments addressed, Dov had needed blood drawn, and the autism grapevine had informed them that Berry was the man to see.

  Bringing Berry into CAN was only one of the steps Jon and Portia took, under Geschwind’s guidance, to professionalize their concept. He schooled the couple on the absolute necessity of maximum consistency in the procedures used to get each sample, and in the way autistic traits were documented in each donating individual. He also explained that researchers would want detailed histories not only of the two or more children in a household with autism, but also of their family members, who shared most of the same DNA. Cure Autism Now’s founders resigned themselves to spending a great deal more money than they initially intended.

  They also hired Catherine Lord, PhD, who came with one of autism’s more gold-plated résumés. She had degrees in psychology from UCLA and Harvard, had done her clinical internship with the famous TEACCH program at the University of North Carolina, and was renowned for helping to develop a new tool for identifying autism in children. The Autism Diagnostic Instrument (ADI) was a specialized questionnaire, directed at parents, to tease out recognition of behaviors in a child that were rare but indicative of autism. The ADI was recognized for its power to yield reliable and consistent results, regardless of the biases of the tester, as long as he or she was well trained in its use. With Cure Autism Now paying the cost, Lord began running workshops to turn a lot of bright, interested students into certified ADI “raters.”

  In 1997, just as their counterparts in New Jersey were handing out the first five NAAR grants, Jon and Portia finally launched the full DNA project, under the acronym AGRE—for the Autism Genetic Research Exchange. Scores of families signed up immediately, their imaginations captured by the possibility of cracking autism’s genetic code. Each received a home visit from one of the new ADI raters, who spent hours interviewing the family. The results, along with audio- and videotapes made during the visit, went back to Los Angeles for analysis. Whenever an autism diagnosis was confirmed, Ed Berry showed up, dropping by after a long train ride and drive, to draw blood in his gentle way from the entire family. Next, Berry shipped the physical blood samples, packed against damage, east to the Rutgers University Cell Repository for perpetual preservation. Once there, each sample underwent genomic screening, as well as a process of “immortalization,” in which copies of the blood’s component cells were manufactured and multiplied to create an indefinite supply identical to the originals.

  This was not a process that moved quickly. It took three years to get the first 150 families through it, at which point another 250 were already in the pipeline. The cost of sustaining the program eventually exceeded more than $1 million annually. But significant support arrived in the form of a multimillion-dollar grant from the National Institutes of Health, which was a major boost to Cure Autism Now. Getting outside money steered to autism had always been one of its goals, and getting that level of financial commitment also proved that it had conquered the quality-control challenge.

  Certainly, the scientific community was convinced. As the collection slowly climbed, passing 540 samples collected in the 2005 edition of its online publication, ADVANCES, researchers from all over the world were calling on the library’s resources regularly and had begun publishing papers crediting Cure Autism Now for their work on autism’s genetics. By then, at least sixty-three authors had cited the database in their publications.

  To be sure, these initial rounds of deeper research into the genomes of diagnosed individuals only confirmed that the “code” everyone wanted to crack was going to be even more complex than anticipated. But even that recognition represented a significant advance.

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  ON THE EAST COAST, as Karen and Eric London had hoped, getting real scientific results from the first round of NAAR-funded studies made it easier to raise funds for the next. Having more funds yielded still more quality research. The virtuous cycle continued. In 1998, the second year of its grant program, NAAR underwrote ten studies in the amount of half a million dollars. In 1999, when proposals came from as far away as Italy and Russia, sixteen recipients received $800,000 in grants and fellowships. The fellowships fulfilled a specific ambition of the Londons. Awarded in chunks of $100,000, split over two years, they were available to young researchers and MDs who were committed to making the biomedical dimension of autism the full-time focus of their developing careers. There was no shortage of applicants. Thanks to the Londons, a new kind of career path was being born as the new millennium began.

  Then the Londons set out to build a library of biological material too. In NAAR’s case, the goal was to create a bank of brain tissue, to permit anatomical research. In most cases, children with autism die unexpectedly—overwhelmingly by drowning or by seizures. NAAR created protocols for making sensitive yet timely approaches to grieving families, suggesting organ donation for the sake of future generations of kids. Over time, word of the tissue bank’s existence spread among America’s autism community and donations increased. Physically stored at the Harvard Brain Tissue Resource Center, the autism brain bank quickly caught the attention of researchers, launching many studies that might never have been undertaken otherwise.

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  TO BE SURE, differences in style would continue to distinguish CAN and NAAR, along with nuances in philosophy. But in reality, as time passed, “Hollywood” and “Princeton” cooperated more than they competed. The two groups coordinated their calendars, so that they were not soliciting research proposals from the scientific community at the same time. They mentioned each other favorably in their respective newsletters and referred prospective researchers to each other when it seemed to be a better match. They scrupulously avoided criticizing each other’s scientific choices in public.

  The autism community had by this time grown accustomed to the idea that there were two organizations taking the lead in biomedical research, bringing about profound and enduring changes in the ways autism was investigated, perceived, and funded for research purposes. Working with nearly identical goals, these two groups inspired scientists from disparate and rarefied branches of research to embrace the mystery of autism as worthy of their time, their energy, and their own big ideas.

  In 2001, NAAR and CAN jointly cosponsored the first International Meeting for Autism Research as an add-on to that year’s conference of the Society of Neuroscience. Nicknamed IMFAR, it was a sign of how successfully the two groups had legitimized autism research that some two hundred scientists from the United States and Canada, who came for the main neuroscience conference, also made time for the autism meeting. This was the same pool of researchers among whom Eric London had strolled only a few years earlier, scanning their posters in vain for any sign of interest in autism and encountering impatience when he tried to bring it up. Now they were interested.

  Those first two hundred scientists were only the start. Over the next few years, as IMFAR became a stand-alone event, researcher attendance doubled, then doubled again, as scientists traveled from six continents to be there. Even news organizations began sending representatives, looking for stories among the hundreds and hundreds of papers, posters, and presentations that scientists had now become eager to publicize.

  For getting all this started—for creating this new scientific attention paid to autism, for getting money to move in that direction, for getting young researchers to make understanding autism the focus of their careers—the credit would always belong to the founders of CAN and NAAR. They pushed the boundaries—which had always existed, and always would, at the point where what was known for cert
ain about autism collided with its persistent mystery. They were forever confounding, these boundaries—to where the experts could never decide for sure where autism’s very outlines were to be found, and such that parents would continue to dream of leaping the mystery’s own frontiers in one jump, as some once thought they could do, with fingers on a keyboard. But those four parents settled instead for the hard work of science. Largely because of what they started in the 1990s, the boundaries of knowledge would continue advancing while the mystery yielded, only little by little, but year by year, to inroads made by solid science.

  But during these same years, and even as early as that first IMFAR conference the parents pulled together in 2001, there was another force in play, which trained a brighter spotlight on the subject of autism than ever before. It wasn’t just scientists paying attention to the condition anymore. For the first time, a much larger public was learning what autism was about, but in ways that moved their response, in remarkably short order, from curiosity to fear.